The proposed studies have two major goals, namely: (1) to establish an animal model of HIV perinatal transmission which can be used to test strategies to interrupt transmission; and (2) to elucidate the timing and mechanism of in utero maternal-fetal transmission. By utilizing a chronically catheterized pregnant macaque and her fetus, the maternal peripheral blood, fetal peripheral blood and amniotic fluid compartments will be simultaneously sampled over time to monitor the viral load, antibody response, and the changes in T cell populations after maternal infection with HIV-2-287. The investigators will then test two hypotheses that: (i) the maternal virologic and immunologic responses (and their time course) can predict transmission; and (ii) that the amniotic fluid exposure is a route of in utero HIV transmission.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL056548-04
Application #
2901245
Study Section
Special Emphasis Panel (SRC (64))
Project Start
1996-04-01
Project End
2001-03-31
Budget Start
1999-04-01
Budget End
2000-03-31
Support Year
4
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Washington
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Ho, Martin T; Kelly, Edward J; Bodor, Miklos et al. (2011) Novel cytochrome P450-2D6 promoter sequence variations in hepatitis C positive and negative subjects. Ann Hepatol 10:327-32
Woodahl, Erica L; Crouthamel, Matthew H; Bui, Tot et al. (2009) MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol 64:183-8
Choi, Sung-Up; Bui, Tot; Ho, Rodney J Y (2008) pH-dependent interactions of indinavir and lipids in nanoparticles and their ability to entrap a solute. J Pharm Sci 97:931-43
Kinman, Loren; Bui, Tot; Larsen, Kay et al. (2006) Optimization of lipid-indinavir complexes for localization in lymphoid tissues of HIV-infected macaques. J Acquir Immune Defic Syndr 42:155-61
Salama, Noha N; Endsley, Aaron; Ho, Rodney J Y (2006) Recent developments in drug targets and delivery of anti-HIV drugs. Infect Disord Drug Targets 6:107-19
Yimam, Mesfin A; Bui, Tot; Ho, Rodney J Y (2006) Effects of lipid association on lomustine (CCNU) administered intracerebrally to syngeneic 36B-10 rat brain tumors. Cancer Lett 244:211-9
Bodor, Miklos; Kelly, Edward J; Ho, Rodney J (2005) Characterization of the human MDR1 gene. AAPS J 7:E1-5
Woodahl, Erica L; Yang, Ziping; Bui, Tot et al. (2005) MDR1 G1199A polymorphism alters permeability of HIV protease inhibitors across P-glycoprotein-expressing epithelial cells. AIDS 19:1617-25
McConnachie, Lisa; Bodor, Miklos; Kowdley, Kris et al. (2004) Human liver cytochrome P450 2D6 genotype, full-length messenger ribonucleic acid, and activity assessed with a novel cytochrome P450 2D6 substrate. Clin Pharmacol Ther 75:282-97
Yang, Ziping; Horn, Micha; Wang, Joanne et al. (2004) Development and characterization of a recombinant Madin-Darby canine kidney cell line that expresses rat multidrug resistance-associated protein 1 (rMRP1). AAPS PharmSci 6:E8

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